Rapid rescreening of cervical smears as a quality control method in a high-risk population

OBJECTIVE: Cancer of the cervix is one of the commonest cancers in South Africa. Accurate cytological diagnosis is one of the prerequisites for an effective cervical screening programme and requires the implementation of appropriate quality assurance modalities. This study was undertaken to determine if rapid review of reportedly negative cervical smears is a useful internal quality assurance modality in an unscreened population with very high rates of cervical carcinoma. METHOD: Approximately 26% of all cervical smears received at the study institution between 1 January 1998 and 31 December 2003, and initially reported as negative or inadequate, underwent rapid review. RESULTS: A total of 62,866 (26%) cervical smears out of 241,796 reportedly negative or inadequate cervical smears underwent rapid review. An amended report was sent out in 373 (0.59%) of these 62,866 cervical smears. This included 101 cases of high-grade squamous intraepithelial lesion (HSIL) and high-grade atypical squamous cells (ASC-H), 143 low-grade squamous intraepithelial lesions, 54 atypical squamous cells of undetermined significance (ASC-US) and 33 atypical glandular cells that were not reported initially. The false-negative proportion for HSIL and ASC-H (combined) in this study was 5.76%. No squamous cell carcinomas were diagnosed on rapid review but one patient with HSIL/ASC-H on review had squamous cell carcinoma on biopsy. Three cytotechnologists had a lower sensitivity of primary screening and required retraining. CONCLUSIONS: Rapid review is beneficial as an internal quality assurance modality in an unscreened high-risk population and increases the detection of women with significant cervical lesions requiring treatment. The relatively low cost of rapid review compared with other rescreening modalities makes this an attractive option in low resource settings.     

Cytopathology of Apple stem pitting virus in Nicotiana occidentalis L.

Apple stem pitting virus (ASPV) is a causal agent of stem pitting associated disease in pomes fruit trees. The present report focuses on a cytopathological effect of ASPV infection in a herbaceous host Nicotiana occidentalis ‘37B’. A leaf dip preparation shows predominantly basic virus particles and aggregated particles 800 nm and 3200 nm long respectively. The main cytopathological effect observed in ASPV infected N. occidentalis includes fibrous aggregates of virus particles (massive/or few), formation of membranous vesicles and proliferation of the endoplasmic reticulum.     

Rapid screening: a comparative study

Although rapid screening of negative and inadequate cervical smears is a quality assurance requirement for all UK laboratories, there has been little attempt to standardize the method and laboratories make use of a number of different techniques and times. The aim of this study was to assess the sensitivity of these various techniques by measuring their ability to pick out known false-negative smears. Completed questionnaires from 123 laboratories across England revealed that 52% of laboratories use a "step" technique, 19% use "turret", 15% use random paths and 34% attempt to rescreen the whole slide quickly. Twenty-two percent of laboratories use a mixture of techniques. Timings are also variable, with the majority of laboratories allowing screeners to review slides at a pace decided by themselves but usually between 1 and 2 min. The study involved 120 participants who performed a total of 24 000 rapid screens. The results showed that, of the 90 abnormal slides used in the study, 62 cases (69%) were identified as abnormal or needing review by more than 50% of participants. Overall rapid screening picked out 58% of high-grade squamous abnormalities, 59% of low-grade abnormalities and 72% of glandular lesions. Step screening performed best, followed by whole slide/random and then turret. One minute was the optimum time and there was a significant fall in performance once individuals attempted to rescreen large numbers (>50). The most significant finding was the marked variation in the performance of individuals using the same slide sets.     

ABC3 Part II: a review of the new criteria for evaluating cervical cytology in England

R.G. Blanks
ABC3 Part II: a review of the new criteria for evaluating cervical cytology in England The new Achievable Standards, Benchmarks for Reporting, and Criteria for Evaluating Cervical Cytopathology, 3rd edn (ABC3) includes radical changes in the criteria for evaluating cervical cytology. First, they include a new mission statement ‘the objective of cervical screening is to reduce cervical cancer incidence and mortality by screening with a high sensitivity for the detection of CIN2 or worse, whilst maintaining a high specificity’. Second, the original four performance measurement criteria where laboratories were examined further if they were below the 10th or above the 90th percentile has been changed to three and laboratories are only mandatorily examined if they fall below the 5th or above the 95th percentile. The old criteria related to the percentage of samples that were inadequate, the percentage of all adequate samples reported as moderate dyskaryosis or worse (equivalent to high‐grade squamous intraepithelial lesion or cancer), the percentage of adequate samples reported as mild dyskaryosis or borderline (equivalent to low‐grade squamous intraepithelial lesion or atypical squamous/glandular cells) and the positive predictive value. The new criteria are percentage of inadequate samples, positive predictive value and a new measure termed referral value. These changes mean that far fewer laboratories will require mandatory examination. Third, a raft of optional performance measures have been introduced to help laboratories examine their annual statistical return to the Department of Health in comparison with other laboratories. These measures have been designed to produce a more uniform national programme, and to help laboratories decide whether they are maximizing the benefit of screening while minimizing the harm, which is the goal of all screening programmes. This review examines in detail the new criteria and explains in more detail some of the thinking behind them.     

Accuracy and perceptions of virtual microscopy compared with glass slide microscopy in cervical cytology

A. Evered and N. Dudding Accuracy and perceptions of virtual microscopy compared with glass slide microscopy in cervical cytology Objective: To evaluate virtual microscopy in terms of diagnostic performance and acceptability among practising cytologists. Methods: Twenty‐four experienced cytologists were recruited to examine 20 SurePath® cervical cytology slides by virtual microscopy. Diagnostic accuracy was compared with glass slide microscopy using an unbiased crossover experimental design. Responses were allocated a score of one for a correct identification of normal or abnormal (borderline/atypical changes in squamous or glandular cells or worse) and a score of zero for an incorrect response (a normal slide reported as abnormal or vice versa). Perceptions of virtual microscopy were assessed by questionnaire analysis. Results: Participants yielded a total of 285 responses for the virtual slide set and 300 for the glass slide set. The approximate time to screen a virtual slide was 18 minutes, compared with 8 minutes or less for a glass slide. Overall there was no significant difference between virtual microscopy and glass slide microscopy in terms of diagnostic accuracy (P = 0.22). Virtual microscopy under‐performed when images were captured over a narrow focal range (P = 0.01). Diagnostic accuracy of virtual microscopy equalled that of glass slide microscopy when participants were able to focus through the full thickness of the slide images (P = 0.07). The most common difficulties experienced by participants with virtual microscopy were freezing of the computer screen during image download, slow response of the computer during slide movement and, in some instances, ‘fuzzy’ images. Cytologists have a strong preference for glass slides over virtual microscopy despite the overall equal diagnostic performance of the two viewing modalities. Conclusions: Diagnostic accuracy of virtual microscopy can equal that of glass slide microscopy. However, without good computer network connections, wide focal range and software that permits effortless navigation across virtual slides, cytologists are unlikely to be convinced of the utility of this technology for cytology screening and diagnosis.     

Analysis of the performance of 100% rapid review using an average time of 1 and 2 minutes according to the quality of cervical cytology specimens

E. J. C. Manrique, N. L. A. Souza, S. B. N. Tavares, Z. B. P. Albuquerque, L. C. Zeferino and R. G. Amaral Analysis of the performance of 100% rapid review using an average time of 1 and 2 minutes according to the quality of cervical cytology specimens Objectives: To compare the performance of the 100% rapid review method carried out in a mean time of either 1 or 2 minutes according to cytological final result, and to assess whether the presence of obscuring factors in cervical smear samples affects the frequency of false‐negative results. Methods: A total of 5 235 smears classified as negative (93.0%) or unsatisfactory (2.1%) at routine screening were submitted to 100% rapid review using mean times of 1 and 2 minutes. Results: Of the 5 235 smears submitted to 1‐minute rapid review, 88 were considered suspect and of these, 45 were confirmed as abnormal in the cytological final result. When the time used was 2 minutes, 67 smears were considered suspect, 44 of which were confirmed as abnormal. Sensitivity and specificity were similar in the 1‐ and 2‐minute reviews. In smears in which samples were satisfactory and had no obscuring factors, sensitivity and specificity were 64.2% and 98.9% and 61.5% and 99.5% for the 1‐ and 2‐minute reviews, respectively. In comparison, in smears in which the sample was satisfactory for analysis but partially obscured (50–75%), sensitivity and specificity were 64.7% and 99.9% and 70.6% and 99.8% for the 1‐ and 2‐minute reviews, respectively. Conclusions: The method of rapid review of 100% showed no difference in the detection of false‐negative results using the time of 1 or 2 minutes. The quality of the sample did not influence the detection of false‐negatives.     

European guidelines for quality assurance in cervical cancer screening: recommendations for cytology laboratories.

The quality of a cervical cytology laboratory depends on adequate handling and staining of the samples, screening and interpretation of the slides and reporting of the results. These guidelines give an overview of procedures recommended in Europe to manage the balance between best patient care possible, laboratory quality assurance and cost effectiveness and will be published as a chapter 4 in the European Guidelines for Quality Assurance in Cervical Cancer Screening. The laboratory guidelines include protocols for personnel and organisation, material requirements, handling and analysing cervical samples, recording of results, quality management and communication. The section on quality management is comprehensive and includes protocols for all aspects of internal and external quality assurance. The guidelines are extensively referenced and as far as possible the recommendations are evidence-based.     

Survey of medical training in cytopathology carried out by the journal Cytopathology

Anshu, A. Herbert, B. Cochand‐Priollet, P. Cross, M. Desai, R. Dina, J. Duskova, A. Evered, A. Farnsworth, W. Gray, S. S. Gupta, K. Kapila, I. Kardum‐Skelin, V. Kloboves‐Prevodnik, T. K. Kobayashi, H. Koutselini, W. Olszewski, B. Onal, M. B. Pitman, ?. Marin?ek, T. Sauer, U. Schenck, F. Schmitt, I. Shabalova, J. H. F. Smith, E. Tani, L. Vass, P. Vielh and H. Wiener
Survey of medical training in cytopathology carried out by the journal Cytopathology This report of the Editorial Advisory Board of Cytopathology gives the results of a survey of medical practitioners in cytopathology, which aimed to find out their views on the current situation in undergraduate and postgraduate training in their institutions and countries. The results show that training in cytopathology and histopathology are largely carried out at postgraduate level and tend to be organized nationally rather than locally. Histopathology was regarded as essential for training in cytopathology by 89.5% of respondents and was mandatory according to 83.1%. Mandatory cytopathology sections of histopathology were reported by 67.3% and specific examinations in cytopathology by 55.4%. The main deficiencies in training were due to its variability; there were insufficient numbers of pathologists interested in cytology and a consequent lack of training to a high level of competence. Pathologists without specific training in cytopathology signed out cytology reports according to 54.7% of responses, more often in centres where training was 3–6 months or less duration. Although 92.2% of respondents thought that specialist cytology should not be reported by pathologists without experience in general cytopathology, that practice was reported by 30.9%, more often in centres with small workloads. The survey report recommends that 6–12 months should be dedicated to cytopathology during histopathology training, with optional additional training for those wanting to carry out independent practice in cytopathology. Formal accreditation should be mandatory for independent practice in cytopathology. When necessary, temporary placements to centres of good practice should be available for trainees intending to practise independently in cytopathology. There should be adequate numbers of pathologists trained in cytopathology to a high level of competence; some of their time could be released by training cytotechnologists and trainee pathologists to prescreen cytology slides and assess adequacy of fine‐needle aspiration samples when immediate diagnosis was not required. The survey demonstrated a clear need for European and international guidelines for training in cytopathology.     

Rapid cervicovaginal smear screening: method of quality control and assessing individual cytotechnologist performance

AIM: To validate the method of rapid screening (RS) in the detection of cervical lesions and false-negative results as well as in quality control of cytotechnologist performance. MATERIAL AND METHODS: The RS method was validated on Papanicolaou-stained and initially conventionally analysed vaginal, cervical and endocervical (VCE) smears collected in an opportunistic programme for the detection of cervical carcinoma. The study included 3680 VCE smears from the Department of Gynaecologic Cytology, University Department of Gynaecology and Obstetrics, Zagreb University Hospital Center, Zagreb and from the Department of Clinical Cytology, Osijek University Hospital, Osijek. Histologically verified abnormal findings accounted for 10% of the study samples. Thirteen cytotechnologists, with no previous experience in RS, performed the test. Each slide was examined using the 'step' technique for 1.5 minutes, the findings were classified as negative or abnormal, and the abnormal ones were also classified according to differential cytological diagnosis. The results were compared with those obtained on initial screening. Abnormal findings from a group of initially negative findings were reanalysed using conventional methods to make definitive cytological diagnosis. RESULTS: RS yielded a sensitivity of 83.7%, specificity of 93.7%, positive predictive value of 62.4%, negative predictive value of 97.9% and diagnostic accuracy of 92.6%. Relative to the initial abnormal differential cytological diagnosis, the diagnostic value of RS increased with lesion severity [54.8%, 68.0% and 91.3% for cervical intraepithelial neoplasia (CIN) I, CIN II and CIN III respectively]. RS detected 38 additional positive findings; 94.2% of these were atypical squamous cells of undetermined significance (ASCUS)/abnormal glandular cells undetermined significance (AGUS) and CIN I. The rate of additional positive findings was 1.14% (38/3135). The false-negative rate of initial screening was 9.4% (38/406), and individual cytotechnologist sensitivity was 60.0-100.0%. CONCLUSION: RS could be introduced as an efficient method of quality control to improve the sensitivity of cytological screening as well as for quality control of cytotechnologist performance.     

The use of digital images to evaluate the interobserver agreement on cervical smear readings in Italian cervical cancer screening

G. Tinacci, A. Biggeri, A. Pellegrini, M.P. Cariaggi, M.L. Schiboni and M. Confortini The use of digital images to evaluate the interobserver agreement on cervical smear readings in Italian cervical cancer screening Objective: The aim of this study was to measure interobserver agreement among cytologists on using a set of digital images. Methods: A set of 90 selected Papanicolaou‐stained cervical smears were digitalized and the digital images circulated among 117 readers, from laboratories spread across almost all Italian regions. Three representative fields of each smear were displayed at 20× and 40× magnification (overall six images for each case). The diagnoses made by the cytologists who provided the images were taken as target diagnoses. Results: The κ values were: very low for the categories atypical squamous cells of undetermined significance (ASC‐US), and atypical squamous cells – cannot exclude high‐grade squamous intraepithelial lesion (ASC‐H); poor for the categories atypical glandular cells (AGC), high‐grade squamous intraepithelial lesion (HSIL) and invasive cancer; and fair to good for the categories negative and low‐grade squamous intraepithelial lesion (LSIL). However, we found a cluster of 42 best concordant readers. The overall κ value and overall weighted κ with the target diagnosis for these 42 readers were 0.45 and 0.66, respectively. This finding is in contrast with the overall κ value and overall weighted κ for the other readers of 0.39 and 0.59, respectively. Conclusions: As this finding is an estimate of the accuracy of the readers, we can infer that it will be very important to reach this level of concordance for all the participating readers. Future effort will facilitate common experiences in order to improve the reproducibility of diagnostic criteria. Digital images could be the key to reach this aim.     

Cytopathology training in the United States – a personal view

In this review we present an outline of cytopathology training in the United States, for a non-US readership.     

European guidelines for quality assurance in cervical cancer screening: recommendations for cervical cytology terminology

There are many different systems of cytology classification used in the member states of the European Union (EU) and many different languages. The following short annexe to Chapter 3 of the European Guidelines for Quality Assurance in Cervical Cancer Screening provides a framework that will allow different terminologies and languages to be translated into standard terminology based on the Bethesda system (TBS) for cytology while retaining the cervical intraepithelial neoplasia (CIN) classification for histology. This approach has followed extensive consultation with representatives of many countries and professional groups as well as a discussion forum published in Cytopathology (2005;16:113). This article will describe the reporting of specimen adequacy, which is dealt with in more detail elsewhere in Chapter 3 of the guidelines, the optional general categorization recommended in TBS, the interpretation/cytology result and other comments that may be made on reports such as concurrent human papillomavirus testing and the use of automation review and recommendations for management. The main categories in TBS will be described in the context of CIN, dyskaryosis and dysplasia terminologies so that all may be translated into the same framework. These guidelines should allow European countries to adapt their terminology in such a way as to make their screening programmes comparable with each other as well as with programmes elsewhere in the world.     

Inadequate cervical smears: results of an educational slide exchange scheme

Fifty-six slides, predominantly inadequate and of varying difficulty, were circulated to 12 laboratories as an educationally based slide exchange scheme. Three slides failed to achieve an agreed majority consensus opinion. Seventy percent of participants agreed with the consensus opinion in 80% of slides. Of the slides originally reported as inadequate, the consensus diagnosis was inadequate in 78%, negative in 12% and abnormal in 10%. The latter included two cases of high-grade dyskaryosis. There was good agreement for the two most frequent causes of inadequacy in submitted slides (obscured and poor cellularity). There was poor consistency in reporting the presence or absence of endocervical and immature squamous metaplastic cells, to an extent that questions their use in the assessment of smear adequacy. Three inadequate slides on consensus opinion were associated with subsequent cervical intraepithelial neoplasia (grade III) or invasive squamous cell carcinoma. In the latter case, the slide had originally been reported as negative by the submitting laboratory.